Acute appendicitis propedeutics and diagnosis by fiona_messe



                                              Acute Appendicitis
                                    – Propedeutics and Diagnosis
                                                                          Andy Petroianu
         Department of Surgery, Medical School of the Federal University of Minas Gerais,

1. Introduction
Appendicitis is the most common abdominal emergency. The lifetime risk of developing
appendicitis is approximately 7% and it is the most common acute abdominal emergency
that requires surgical treatment. The overall incidence of this condition is approximately 11
cases per 10,000 population per year. Acute appendicitis may occur at any age, although it is
relatively rare at the extremes of age. There is an increased incidence in patients between the
ages of 15 and 30 years during which time the incidence increases to 23 per 10,000
population per year; thereafter, the disease incidence declines with age. [1,2,3,4,5,6]
A male preponderance exists, with a male to female ratio of 1.1 to 3:1; the overall lifetime
risk is 9% for males and 6% for females. A difference in diagnostic error rate ranges from
12% to 23% for men and 24% to 42% for women. Most of patients are of white skin colours
(74 %) and is very rare in black skin colour (5 %). [1,2,3,7]
While the clinical diagnosis may be straightforward in patients who present with classic
signs and symptoms, atypical presentations may result in diagnostic confusion and delay in
treatment. [8]

2. Historical aspects
Appendicitis was rare in the past. There appears to be no record of early physicians, from
Hippocrates to Moses Maimonides. The first anatomic drawings of the appendix date back
to circa 1492 when Leonardo Da Vinci described an earlike structure he termed the orecchio
arising from the caecum. Berengario Da Carpi, a physician-anatomist, made his description
of the appendix in 1521. In 1543, Andreas Vesalius published the first detailed illustration of
an appendix. [1]
After the studies of Morgagni, published in 1719, little additional information regarding the
gross anatomy of the appendix was added. Although the anatomy of the appendix was
clearly defined by these early anatomists, its pathology and treatment remained
controversial for the next 300 years. [9]
Jean Fernel, the French court physician to Catherine de Medici, has been credited with the
first description of acute typhlitis (derived from the Greek typhlon for caecum) in 1554 that
occurred in a 7-year-old girl who died of a perforated appendix. At autopsy, Fernel noted
luminal obstruction of the caecum and appendix with necrosis, perforation, and spillage of
contents into the abdominal cavity. Other physicians, surgeons and anatomists described
172                  Inflammatory Diseases – Immunopathology, Clinical and Pharmacological Bases

diseases on this organ. Even the great physiologist John Hunter described a gangrenous
appendix, encountered at an autopsy that he performed on Colonel Dalrymple in 1767.
In 1711, Lorenzo Heister, a professor of surgery at Helmstedt, was the first to suggest the
appendix as the likely site of primary inflammation and abscess formation in acute
typhlitis. Claudius Amyand, Sergeant Surgeon to George II, performed the first known
appendectomy in 1735. Early reports of perityphlitis and typhlitis in the 19th century
appeared to describe a new clinical phenomenon. In 1839, Bright and Addison, the great
physicians of Guy's Hospital, clearly described the symptoms of appendicitis and stated
that the appendix was the cause of many inflammatory processes of the right iliac fossa.
It has been 125 years since Reginald Heber Fitz first described the relationship between
appendicitis with perforation, presenting as a right lower quadrant abscess. Fitz was the
Shattuck Professor of Pathological Anatomy at Harvard University. On June 18, 1886, he
presented a paper to the Association of American Physicians in Washington, D.C., entitled
“Perforating inflammation of the vermiform appendix with special reference to its early
diagnosis and treatment”. He went on to describe the clinical features of appendicitis and
proposed early surgical removal of the appendix. His remarks led to the increasing
recognition of appendicitis as an important clinical entity and appendectomy as its
appropriate treatment. Willard Parker of New York, published a paper in 1867 recounting
his experiences, beginning in 1843, with drainage of appendiceal abscesses. [9,10,11]
The first known surgical removal of the appendix occurred in 1735. Claudius Amyand, a
founder of St. George's Hospital in London, operated on an 11-year-old boy with a
longstanding scrotal hernia and a faecal fistula of the thigh. Through a scrotal incision, the
hernia was opened, revealing omentum surrounding an appendix that was perforated by a
pin, giving rise to the faecal fistula. The appendix and omentum were amputated, and the
fistula opened with recovery. [9]
In 1880, Lawson Tait operated on a 17-year-old girl, removing a gangrenous appendix.
Abraham Groves of Fergus, from Ontario. removed an inflamed appendix from a 12-year-
old boy with pain and tenderness in the right lower quadrant of the abdomen in 1883. In
1884, Mikulicz performed an appendectomy, but the patient did not survive. In 1885,
Kronlein of Zurich successfully performed an appendectomy. Also in 1885, Charter-
Symonds of London performed such an operation. Thomas G. Morton of Philadelphia, in
1887, reported a successful appendectomy with drainage of an abscess in a 27-year-old
patient. With the advocacy of early surgical intervention, the mortality rate of acute
appendicitis over the 15 years succeeding Fitz's manuscript dropped from 50% to 15%.
In a presentation to the New York Surgical Society in 1889, Charles McBurney described his
experience with many successful operations for early removal of the appendix. He also
described his, now famous, McBurney's point. Their surgical aim was to operate in a timely
fashion before appendiceal perforation and peritonitis developed. The early clinical
diagnosis and operative intervention recommended by McBurney over a century ago
remains the standard of care for the practicing emergency physician today. The lateral
muscle-splitting or "gridiron" incision is generally called the McBurney incision, however it
was used firstly by Lewis McArthur of Chicago, and was described in 1894. J. W. Elliot
advocated a transverse skin incision in 1896. [1,5,8,9,10]
Acute Appendicitis – Propedeutics and Diagnosis                                            173

Nothing new happened for almost 90 years until Semm, a German gynaecologist, removed
an appendix, in 1980, by a laparoscopic approach. During almost one decade he was
disbelief in the surgical community, but today this is considered the best surgical approach
to the appendix. [10,13,14]
The idea that appendicitis may resolve spontaneously is not new. In 1908 Alfred Stengel
wrote: “Treated in a purely medical or tentative manner, the great majority of patients with
appendicitis recover”. The first successful instances of the nonoperative medical treatment
of appendicitis occurred on board US Navy submarines during combat patrol in World War
II. The practice of nonoperative medical treatment of appendicitis continued successfully on
board US Navy submarines after the end of this war. The first report on the non-operative
management of appendicitis was published by Coldrey in 1959. Thirteen additional cases of
appendicitis were treated medically from 1960 to 1964 on board US Navy Polaris
submarines. There were two failures (15.4%) resulting from gangrenous appendicitis (one
medically evacuated and one appendectomy performed on board with great difficulty).

3. Anatomy
Embryologically, the appendix is part of the caecum from which it originates where the
three taeniae coli coalesce at the distal aspect of the caecum. In addition, the appendix
contains an abundance of lymph follicles in the submucosa, numbering approximately 200.
The highest number of lymph follicles occurs in the 10- to 20-year-old age group; they
decline in number after age 30 and are totally absent after age 60. [5]
The adult appendix is a long diverticulum averaging 5 to 10 cm in length that arises from
the posteromedial wall of the caecum, approximately 3 cm below the ileocaecal valve. The
mean width is 0.5 to 1.0 cm. Although the relationship of the base of the appendix to the
caecum essentially is constant, the remainder of the appendix is free, which accounts for its
variable location in the abdominal cavity. The orientation of the appendix in the abdomen
has classically been described as lying in the right lower quadrant, at a position
approximately one-third the distance from the right anterior superior iliac spine to the
umbilicus. This region is also known as McBurney's point. [2]
The various positions of the appendix are conveniently categorized into the following
locations: [5,8,18]
-    paracolic - the appendix lies in the right paracolic gutter lateral to the caecum (35 %);
-    retrocaecal - the appendix lies posterior to the caecum and may be partially or totally
     extraperitoneal (30 %);
-    preileal - the appendix is anterior to the terminal ileum (1,5 %);
-    postileal - the appendix is posterior to the ileum (1,5 %);
-    promontoric - the tip of the appendix lies in the vicinity of the sacral promontory (1%);
-    pelvic - the tip of the appendix lies in or toward the pelvis (30%);
-    subcaecal - the appendix lies inferior to the caecum (1 %).
This variability in location may greatly influence the clinical presentation in patients with
appendicitis. A more recent imaging-based study showed that in only 4% is the appendix
located at the classic McBurney point (the junction of the lateral and middle third of the line
between the anterior superior iliac spine and the umbilicus). [5,8,18]
174                  Inflammatory Diseases – Immunopathology, Clinical and Pharmacological Bases

Fig. 1. An appendix being removed through an incision on the McBurney's point.

4. Pathophysiology
The function of the appendix is not clearly understood, although the presence of lymphatic
tissue suggests a role in the immune system. In humans it is regarded as a vestigial organ,
and acute inflammation of this structure is called acute appendicitis. The appendicitis may
be classified into the following terminology: [1]
-    simple appendicitis - inflamed appendix, in the absence of gangrene, perforation, or
     abscess around the appendix;
-    complicated appendicitis - perforated or gangrenous appendicitis or the presence of
     periappendiceal abscess.
The relatively high-refined, low-fibre diet of industrialized countries has been implicated as
an aetiologic factor in the development of appendicitis. The primary pathogenic event in the
majority of patients with acute appendicitis is believed to be luminal obstruction. This may
result from a variety of causes, which include faecaliths, lymphoid hyperplasia, foreign
bodies, parasites, and both primary (carcinoid, adenocarcinoma, Kaposi sarcoma, and
lymphoma) and metastatic (colon and breast) tumours. Faecal stasis and faecaliths may be
the most common cause of appendiceal obstruction, followed by lymphoid hyperplasia,
vegetable matter and fruit seeds, barium from previous radiographic studies and intestinal
worms (especially ascarids). The prevalence of appendicitis in teenagers and young adults
suggests a pathophysiologic role for lymphoid aggregates that exist in abundance in the
appendix in this age group. [5,8,18]
According to this theory, obstruction leads to inflammation, rising intraluminal pressures,
and ultimately ischemia. Subsequently, the appendix enlarges and incites inflammatory
changes in the surrounding tissues, such as in the pericaecal fat and peritoneum. If
untreated, the inflamed appendix eventually perforates. True appendiceal calculi (hard,
noncrushable, calcified stones) are less common than appendiceal faecaliths (hard but
Acute Appendicitis – Propedeutics and Diagnosis                                            175

crushable concretions) but have been associated more commonly with perforating
appendicitis and with periappendiceal abscess. This aetiology of occlusion appears to be
more common in younger individuals, in whom lymphoid tissue is more abundant than in
older persons. [1,2,5,8,18]
Rapid distension of the appendix ensues because of its small luminal capacity and
intraluminal pressures can reach 50 to 65 mm Hg. As luminal pressure increases, venous
pressure is exceeded and mucosal ischemia develops. Once luminal pressure exceeds 85 mm
Hg, thrombosis of the venules that drain the appendix occurs and in the setting of continued
arteriolar inflow, vascular congestion and engorgement of the appendix become manifest.
Lymphatic and venous drainage is impaired and ischemia develops. Mucosa becomes
hypoxic and begins to ulcerate, resulting in compromise of the mucosal barrier and leading
to invasion of the appendiceal wall by intraluminal bacteria. Most of bacterias are gram-
negative, mainly Escherichia coli (present in 76 % of cases), followed by Enteroccocus (30 %),
Bacteroides (24 %) and Pseudomonas (20%).
This inflammation extends to include serosa, parietal peritoneum, and adjacent organs. As a
result, visceral afferent nerve fibres that enter the spinal cord at T8 - T10 are stimulated,
causing referred epigastric and periumbilical pain represented by these dermatomes. At this
stage, somatic pain supersedes the early referred pain, and patients usually undergo a
shifting of maximal pain to the right lower quadrant. If allowed to progress, arterial blood
flow is eventually compromised, and infarction occurs, resulting in gangrene and
perforation, which usually occurs after 24 and 36 hours. Anorexia, nausea, and vomiting
usually follow as the pathophysiology worsens. [1,3,5]
There is strong epidemiologic evidence supporting the proposition that perforated and non-
perforated appendicitis are separate entities with different pathogenesis. Patients with a
short duration of symptoms had a predominantly neutrophil infiltrate that changed to a
predominant lymphocytic infiltrate with evidence of granulation tissue as the duration of
symptoms became longer. These findings support the contention that a mixed infiltrate of
lymphocytes and eosinophils represents a regression phase of acute appendicitis. Fibrous
adhesion formation and scarring of the appendix wall also have been demonstrated and are
consistent with resolution of a previous attack of appendicitis. To understand this
phenomenon, we need to re-examine the pathogenesis of appendicitis. [17]
Even being logical and possible to be true, this theory was not proven. In the most recent
review on aetiology and pathogenesis, several studies showed that, contrary to common
thinking, obstruction of the appendix is unlikely to be the primary cause in the majority of
patients. An investigation that measured the intraluminal pressure in the appendix showed
that in 90% of patients with phlegmonous appendicitis, there was neither raised
intraluminal pressure nor signs of luminal obstruction. There were signs of obstruction of
the appendiceal lumen, expressed as an elevated intraluminal pressure, in all patients with a
gangrenous appendix, but not in patients with phlegmonous appendix. These data suggest
that obstruction is not an important factor in the causation of acute appendicitis, although it
may develop as a result of the inflammatory process. On the basis of available evidence, it is
likely that there are several aetiologies of appendicitis, each of which leads to the final
pathway of invasion of the appendiceal wall by intraluminal bacteria. [17]
Occasionally, patients will complain of pain that is intermittent over the course of weeks or
months. Others may describe a more persistent pain lasting a similar period. At laparotomy,
the appendices of these patients demonstrate histological evidence of chronic active
176                  Inflammatory Diseases – Immunopathology, Clinical and Pharmacological Bases

inflammation or fibrosis supportive of the diagnosis of recurrent or chronic appendicitis.
Recurrent and chronic forms of appendicitis also have been recognized and occur with an
approximate incidence of 10% and 1%, respectively. [1,3,8]
Recently, with the advent of neurogastroenterology, the concept of neuroimmune
appendicitis has evolved. After a previous minor bout of intestinal inflammation, subtle
alterations in enteric neurotransmitters are seen, which may result in altered visceral
perception from the gut; this process has been implicated in a wide range of gastrointestinal
conditions. Further work is needed to determine if the clinical entity of “neuroimmune
appendicitis” truly exists, but it remains an interesting area. [7]
About 95% of serotonin in the body is in the gastrointestinal tract, located mainly in the
mucosal neuroendocrine cells. Large amounts of 5-HT are present in the mucosa of the
appendix where the amine is concentrated in the enterochromaffin cells of the mucosa.
There are two types of neuroendocrine cells in the epithelium: enterochromaffin cells, which
are found as single cells within the crypt cells, and subepithelial neuroendocrine cells,
located in the lamina propria. These cells are recognized by expression of several markers,
including large dense core vesicles containing serotonin and chromogranin A, and synaptic-
like microvesicles containing synaptophysin. 5-HT secretion from enterochromaffin cells
occurs predominantly at the interstitial side and is controlled by a complex pattern of
receptor-mediated mechanisms. [19,20]
Serotonin is involved in diverse motor, sensory, and secretory functions via its different
receptors locating on epithelial cells and on submucosal and myenteric neurons.
Appendixes with inflammation are markedly depleted of serotonin, in the epithelium
(enterochromaffin cells) and lamina propria. [20]
Local increase in serotonin secretion in the appendix may play an important role in the
pathogenesis of inflammation in the appendix. The initial event in appendicitis is thought
to be luminal obstruction with various aetiologies. Once obstruction occurs, epithelial
mucosal secretions increase the luminal pressure. It has been suggested that
enterochromaffin cells have pressure receptors and that upon sensing luminal pressure
they release 5-HT into the lamina propria. After 5-HT is released into the circulation, it is
metabolized in the liver to 5-HIAA by mitochondrial monoamine oxidase, then
subsequently excreted in urine [20,21]
Serotonin is a potent intestinal secretory agent and can cause increased fluid and electrolyte
secretion via the 5-HT3 receptor. Serotonin is also a vasoconstrictor, acting through 5-HT1
and 5-HT2b receptors. By stimulating some atypical receptors, 5-HT mediates endothelium-
dependent relaxing effects on the veins. In addition, through 5-HT4 receptors located in the
myenteric plexus and smooth muscle, serotonin can regulate peristaltic actions in the
alimentary tract. It may be postulated that local serotonin release exacerbates intraluminal
secretion, venous engorgement, vasoconstriction and smooth muscle contraction, which
diverts the congestive process to an inflammatory one. Abundant 5-HT3 receptors on vagal
and other splanchnic afferent neurons and on enterochromaffin cells have a significant role
in inducing nausea and emesis. However, a cause and effect relationship between
subepithelial neurosecretory cells and appendicitis, if any, remains to be established.
The origin of enterochromaffin cells is controversial. Several theories suggest their origin
being as follows: [22]
Acute Appendicitis – Propedeutics and Diagnosis                                              177

-    in the amine precursor uptake and decarboxylation cell (APUD) system;
-    two independent cell origins for mucin-producing cells and carcinoid cells;
-    subepithelial neurosecretory cells (SNC) origin;
-    bidirectional differentiation of a common cell origin;
-    crypt cell origin derived from a population of lysozyme-containing goblet cells present
     in normal intestinal crypts;
-    amphicrine cell origin defined as a cell in the gastrointestinal tract which contains
     mucus granules, zymogen granules, and endocrine secretory which contains mucus
     granules, zymogen granules, and endocrine secretory granules and possesses a
     endocrine-exocrine nature.
As it can be observed, based on the large amount of studies related to appendicitis, it is not
established the pathophysiology of this disease. There is not doubt that all these phenomena
are related to appendicitis and they are part of the genesis of this inflammation. However
more investigations must be performed in order to understand this still mysterious

5. Clinical aspects
Abdominal pain is the primary presenting complaint of patients with acute appendicitis.
The diagnostic sequence of colicky central abdominal pain followed by vomiting with
migration of the pain to the right iliac fossa is present in only 50% of patients. Typically, the
patient describes a peri-umbilical colicky pain, which intensifies during the first 24 hours,
becoming constant and sharp, and migrates to the right iliac fossa. The initial pain
represents a referred pain resulting from the visceral innervation of the midgut, and the
localised pain is caused by involvement of the parietal peritoneum after progression of the
inflammatory process. Loss of appetite is often a predominant feature. Constipation and
nausea are often present with profuse vomiting that may indicate development of
generalised peritonitis after perforation but is rarely a major feature in simple appendicitis.
(Table 1) [1,2,3,5,8,18]

CLINICAL FINDING                                                ADULTS           CHILDREN
Right lower quadrant pain                                         8.4                 —
Migration (periumbilical to right lower quadrant)                 3.6             1.9 to 3.1
Initial clinical impression of the surgeon                        3.5             3.0 to 9.0
Psoas sign                                                        3.2                2.5
Fever                                                             3.2                3.4
Pain before vomiting                                              2.7                 —
Rebound tenderness                                                2.0                3.0
Rectal tenderness                                                 —                  2.3
Table 1. Accuracy (likelihood ratio) of findings from the history and physical examination in
the diagnosis of appendicitis in adults and children. [1,2,3,30]
Patients with acute appendicitis usually are afebrile or have a low-grade fever. Perforation
should be suspected whenever a patient's temperature exceeds 38.3°C. If perforation does
occur, periappendiceal phlegmon or abscess will result if the terminal ileum, caecum, and
omentum are able to “wall off” the inflammation. Peritonitis usually develops if there is free
perforation into the abdominal cavity. (Table 1) [1,2,3,8]
178                   Inflammatory Diseases – Immunopathology, Clinical and Pharmacological Bases

Acute appendicitis should not be considered as a uniform disease in all patients. Particular
manifestations of this inflammation have been described in special conditions that may
bring up confusing or facilitating factors to make an early and precise diagnosis.

5.1 Pregnancy
Appendicitis is the most common extra-uterine surgical emergency in pregnancy, with an
incidence of approximately 1 in 1200 to 1500 pregnancies. Although the symptoms of acute
appendicitis are similar to those in non-pregnant women, nausea, vomiting, and anorexia
may be mistakenly attributed to the pregnancy, particularly in the first trimester. Fever and
tachycardia may not be present during pregnancy. Right upper quadrant pain, uterine
contractions, dysuria, and diarrhoea can also be present. [3,4]
The diagnosis is often delayed due to the high prevalence of background gastrointestinal
complaints, as well as difficulties in the interpretation of physical and laboratory work-up.
Anatomic alterations in the location of appendix due to the expanding uterus and
physiologic changes observed in pregnancy, such as leukocytosis, can hinder the diagnosis.
In addition, there is generally a greater reluctance to operate unnecessarily on a gravid
patient. [25,26]
Considering differential diagnosis, both obstetrical and gynaecological conditions can
present with abdominal pain and mimic appendicitis. Non-obstetrical/non-gynaecological
conditions include gastroenteritis, urinary tract infections, pyleonephritis, cholecystitis,
cholelithiasis, pancreatitis, nephrolithiasis, hernia, bowel obstruction, carcinoma of the large
bowel, mesenteric adenitis, and rectus hematoma, pulmonary embolism, right-lower-lobe
pneumonia, and sickle cell disease. Gynaecologic and obstetric conditions include ovarian
cyst, adnexal torsion, salpingitis, abruptio placenta, chorioamnionitis, degenerative fibroid,
ectopic pregnancy, preeclampsia, round ligament syndrome, and preterm labour. [27]
Laboratory evaluation may not be helpful and cannot be relied on. Leukocytosis in
pregnancy can be as high as 16,000 cells/ml and still considered a normal variant and not a
clear indicator of appendicitis. During labour, it may rise to 30,000 cells/ml, and not all
pregnant patients with appendicitis have leukocytosis. It is not a reliable marker, as up to
33% of cases may have a leukocyte count greater than 15,000/mm. To confirm the diagnosis,
ultrasound has shown to be highly sensitive and specific although to a lesser degree after a
gestational age of 35 weeks due to technical difficulties. This non-invasive procedure should
be considered first in working up suspected acute appendicitis. [7,27]
Incidence rates in the first trimester range from 19% to 36%, in the second trimester, range
from 27% to 60% and in the third trimester, range from 15% to 59%. Due to the lack of
specificity of the preoperative evaluation; the pathologic diagnosis of appendicitis is
confirmed in only 30% to 50% of cases, considering first trimester yields a greater accuracy.
Patients in the second and third trimester of pregnancy often have pain in the right upper
quadrant or flank, with biliary colic and pyelonephritis representing common misdiagnoses.
The risk of delay in diagnosis is associated with a greater risk of complications such as
perforation, infection, preterm labour, and risks of fetal or maternal loss. Maternal mortality
has been reported from none to 2%. An unruptured appendix carries a fetal loss of 1.5% to
9%, while this rate increases up to 36% with perforation. The risk of fetal loss associated with
appendicitis in pregnancy is 33 % in the first trimester, 14 % in the second trimester and
none in the third trimester. [7,27]
Acute Appendicitis – Propedeutics and Diagnosis                                             179

Accordingly, the incidence of perforation during pregnancy is as high as 25% to 55%
compared with 4% to 19% of the general population. With early surgical intervention,
morbidity and mortality rates are similar to those of the non-pregnant patient. Foetal
mortality rates, however, are as high as 35% in patients with perforation and peritonitis,
making early diagnosis and surgery imperative. [1,26,27]
Tests that are used to improve diagnostic performance include compression graded
ultrasonography, magnetic resonance imaging (MRI), and computed tomography (CT).
Radiation exposure also is an important factor in managing pregnant patients. Fetal
exposure from abdominal multidetector CT performed in the first trimester may double the
likelihood of childhood cancer (from 1 to 2 in 600). Consequently, ultrasound is usually the
first study attempted. Compression graded ultrasonography has long been the preferred test
and is indicated first in the work-up of pregnant patients with suspected appendicitis since
there is no exposure to ionizing radiation. However, ultrasonography is operator dependent
and can be difficult to interpret due to obesity, a retrocaecal appendix, or a gravid uterus.
Accordingly, the reported diagnostic performance of ultrasonography in pregnancy varies
widely. Although high accuracy of ultrasound in pregnancy has been reported, several
factors limit its usefulness. The appendix may be displaced from its expected location by the
gravid uterus. The enlarged uterus also may make graded compression difficult.
Due to this variable performance, the use of MRI and CT in pregnant women with suspected
appendicitis has recently gained importance and is advocated by some authors after
normal/inconclusive ultrasonography result. MR imaging has emerged recently as a useful
second-line technique and seems to have a high accuracy and low failure rate. The use of
MR imaging eliminates radiation exposure of the foetus, avoids the operator dependency of
ultrasound, and facilitates rendering alternative diagnoses, such as ovarian torsion or renal
obstruction. However MRI is not free of risks including the potential biological effects of the
static and time-varying magnetic fields, the heating effects of the radiofrequency pulses, and
the acoustic noise generated by the spatial encoding gradients. [18,25,28]
When appendicitis is suspected, timely obstetric as well as a general surgical consult is
necessary. Assessment for open laparotomy is dependent on gestational age since the
appendix progressively relocates. Pregnancy is not considered to be a contraindication for
laparoscopic approach to appendectomy.
Laparoscopic surgery in the pregnant patient has not been broadly accepted in the latter
second and third trimester due to the concern regarding fetal wastage, the effects of carbon
dioxide on the developing foetus and the long-term effects of this exposure. Laparoscopy
procedures take approximately 50% longer with conflicting studies showing decreased length
of stay and hospitalization. Questions arise regarding the risk for decreased uterine blood flow
due to increased intraabdominal pressures from insufflation and the possibility of fetal carbon
dioxide absorption. Use of nitrous oxide pneumoperitoneum has been advocated although
technical difficulties arise with the gravid uterus. Blind placement of the Veress needle, or
primary port, has resulted in puncturing and subsequent pneumoamnion. [29]

5.2 Children
Appendicitis is the most common surgical disease of the abdomen in children. Paediatric
appendicitis varies considerably in its clinical presentation, contributing to delay in
diagnosis and increased morbidity. The methods of diagnosis and treatment of appendicitis
also vary significantly among clinicians and medical canters according to the patient clinical
180                      Inflammatory Diseases – Immunopathology, Clinical and Pharmacological Bases

status, the medical centre's capabilities, and the physician’s experience and technical
expertise. Recent trends include the increased use of radiologic imaging, minimally invasive
and nonoperative treatments, shorter hospital stays, and home antibiotic therapy. Little
consensus exists regarding many aspects of the care of the child with complicated
appendicitis. [1]
In adults, right lower quadrant pain and migration of pain from the umbilicus area to the
right lower quadrant are the symptoms that best predict appendicitis, whereas the absence
of pain before vomiting greatly reduces the likelihood of appendicitis. The accuracy of
history and physical examination findings is somewhat different in children. Vomiting,
rectal tenderness, rebound tenderness, and fever are more helpful (greater positive
likelihood ratio) in children than in adults, whereas right lower quadrant tenderness is
somewhat less helpful. (Table 1) [1,2,3,30,31,32]
Emergency department evaluation of children with acute appendicitis presents a
particular challenge. The rate of misdiagnosis is as high as 57% in children under the age
of 6 years with perforation rates as high as 90% in some series. Common misdiagnoses
include acute gastroenteritis, viral respiratory syndromes, and urinary tract infection.
Children are more likely to complain of diffuse rather than referred or localized pain.
Those initially misdiagnosed tend to have a higher incidence of vomiting, diarrhoea,
constipation, dysuria, and respiratory symptoms accounting for physician bias against the
correct diagnosis.
Perforation is most common in young children, with rates as high as 82% for children under
age 5 years and up to 100% in one-year-olds. A high index of suspicion combined with a low
threshold for surgical consultation minimizes the risk of missed diagnosis. The high
perforation rate in young children is largely due to the fact that they are less communicative
than older children, and their caregivers often assume that their child has gastroenteritis
based on the common accompanying symptoms of anorexia, vomiting, diarrhoea, and fever.
The Alvarado score has been prospectively validated in several populations of children and
adults. Variations include the modified Alvarado score, in Paediatric Appendicitis Score,
which substitutes right lower quadrant pain with cough, hopping, or percussion for
rebound tenderness. However, these modifications have not been shown to perform better
than the original Alvarado score. (Tables 1 and 2) [12,31]

CLINICAL FINDING                                                                     POINTS
Migration of pain to the right lower quadrant                                            1
Anorexia                                                                                 1
Nausea and vomiting                                                                      1
Tenderness in the right lower quadrant                                                   2
Rebound pain                                                                             1
Elevated temperature (≥ 99.1° F = 37.3° C)                                               1
Leukocytosis ( ≥ 10,000 white blood cells per mm3 )                                      2
Shift of WBC count to the left ( > 75 percent neutrophils )                              1
*Patients with a score of > 7 points have a high risk of appendicitis.
*Patients with a score of <5 points have a very low risk of appendicitis.
Table 2. Alvarado score for the diagnosis of appendicitis. [12,33]
Acute Appendicitis – Propedeutics and Diagnosis                                             181

The clinical condition of a child at the time of diagnosis can vary substantially across a
spectrum of severity, from minimally symptomatic children with normal laboratory studies
to those with bowel obstruction and frank septic shock. Surgery is indicated in all cases.
Non-operative treatment should not be proposed in children due to higher risk of severe
complications. Even in children the laparoscopic approach has been preferred not only to
confirm the diagnosis but also to treat the patient. [31]

5.3 Elderly
Patients at the extremes of the age spectrum can present diagnostic difficulty because of
non-specific presentation, often with subtle clinical signs. Elderly people may present with
confusion. A high index of suspicion for acute appendicitis is needed in such patients. Older
patients present later, have more subtle signs and symptoms, and often treat themselves
with analgesics before their presentation. [1]
Those at the extremes of age appear to be at highest risk of perforation from delayed
diagnosis. The proportion of perforations has a relation to age, with a high proportion in
older people. Misdiagnosis commonly exceeds 50%, with perforation rates that range from
40% to 70%. Delay because of atypical presentation and age-related differences in the
progression of the inflammation have been proposed as explanations. The high proportion
of perforated appendicitis in older patients is therefore the consequence of the relatively low
incidence rate of non-perforated appendicitis at these ages and is not associated with an
increased incidence rate of perforations. [15]
The inflammatory process is less intense than in the youth and occurs later. On the other
hand, the appendicitis in the elders is mainly due to ischemic phenomena with early
necrosis and perforation. Thus these patients present early appendiceal perforation, before
the inflammatory process is developed. The less intense inflammation and the ischemic
process are responsible for the poor abdominal symptoms and laboratorial or
imaginological findings.
Elderly patients may present with vague abdominal pain or even no pain at all. With the
age-related increased risk of other pathologic entities, such as diverticulitis and cancer, the
diagnosis of appendicitis is often delayed up to 72 hours. [2]
Patients over the age of 55 years underwent laparotomy on average two days later than
youth people and with higher risk of severe complications. For these reasons and
considering the elder people have less organic reserve, the surgery is indicated precociously.
The laparoscopy is indicated to confirm the diagnosis and perform the appendiceal
withdrawn. Even when the appendix is perforated, the laparoscopy is the best procedure
since the patients does not present abdominal multiple adhesions provoked by previous
surgeries. Due to pneumoperitoneum, this approach should be carefully considered in
patients with severe heart and pulmonary disturbances.

5.4 Haematological diseases
Patients suffering of some haematological diseases, such as drepanocitosis, spherocytosis,
neutropenia, leukaemia and thrombocitopenic purpura present a higher incidence of acute
appendicitis. It is not established the pathophysiology of these conditions related to the
development of appendicitis.
In fact, inflammation is not the main finding in these cases. Similarly to elder patients in the
presence of haematological diseases the appendix present vascular obstructions with ulcers
182                  Inflammatory Diseases – Immunopathology, Clinical and Pharmacological Bases

spread in its mucosa. Due to ischemia, transmural necrosis is frequent and perforation
occurs earlier and most frequently than in the general population. Thus a special attention to
the appendix should be considered when these patients complain abdominal pain, even
without the characteristics events found in the classical appendicitis provoked by
inflammatory phenomena.
The surgical treatment should be considered even before the confirmation of the diagnosis,
when the patient persists with pain or his general state worsens. In all cases the appendix
should be removed.

5.5 Oncological diseases
Patients undergoing chemotherapy for solid tumours or leukaemias also present a clinical
dilemma. During the induction of therapy, many patients experience abdominal pain.
Although a majority of these patients have self-limiting symptoms, others develop
progressive abdominal pain. Among the most common identifiable source of pain is acute
typhlitis, inflammation of the terminal ileum and caecum.
Abdominal pain is a common complication of chemotherapy, almost unique to children, and
is usually treated non-surgically. Differentiation from acute appendicitis, however, is
extremely difficult, with a documented error rate in these patients of greater than 37%. In
order to avoid the unacceptably high morbidity and mortality associated with the peri-
operative complications of perforation, exploration has been recommended in these patients
with early signs suggestive of local peritonitis.
All these patients are immunocompromised and the mortality of complicated appendicitis is
higher than in the general people. Thus the appendectomy should be precociously indicated
when acute appendicitis is clinically suspected.

5.6 AIDS
Patients with AIDS present a higher incidence of appendicitis than the general population. It
is not established this complication is due to local infection in this immunocompromised
group or is consequent to ischemic factors.
In most of patients (91 %) the pain is localized in the right flank, but 24 % of them complain
general abdominal pain since the beginning. Anorexia is found in 90 % of patients. Nausea
and vomiting are present in 41 % and intensification of diarrhoea occurs in 22 % of these
Immunocompromised patients are at particular risk of developing complications from
delayed diagnosis. These patients present with signs and symptoms of acute appendicitis;
however, there may be a delay in seeking evaluation because pain tolerance is higher or
analgesic drugs may be readily available.
Patients with the acquired immunodeficiency syndrome (AIDS) commonly have symptoms
in the gastrointestinal system. Opportunistic infections such as cryptosporidiosis,
cytomegalovirus colitis, Mycobacterium avium intracellulare, and lymphoma and Kaposi's
sarcoma may present similarly to acute appendicitis, making the diagnosis difficult. The
perforation rate is approximately 40% in this population and recommends early surgical
intervention. [1]

6. Diagnosis
The diagnosis of appendicitis can be challenging even in the most experienced of clinical
hands. The diagnosis of acute appendicitis is predominantly a clinical one. An accurate
Acute Appendicitis – Propedeutics and Diagnosis                                           183

diagnosis is important to prevent unnecessary surgery and avoid complications. The
probability of appendicitis depends on patient age, setting, and symptoms. The probability
of appendicitis depends on patient age, setting, and symptoms. [30,33]
The Alvarado score, originally described in 1986, is the most widely reported scoring system
for acute appendicitis. This score alone is not accurate enough to diagnose or exclude
appendicitis. (Table 2) However, it provide a useful starting point by identifying children
and adults at low and high risk of appendicitis. Most patients at low risk can be observed
without further diagnostic study, but they may benefit from further diagnostic testing,
including imaging studies; and patients at high risk should receive urgent surgical
evaluation. Five percent of patients with scores of 3 or less have appendicitis, 36% of
patients with scores between 4 and 6 have appendicitis, and 78% of patients with scores of 7
or higher have appendicitis. [12,33]
No specific diagnostic test for appendicitis exists, but the judicious use of simple urine and
blood tests, particularly inflammatory response variables, should allow exclusion of other
pathologies and provide additional evidence to support a clinical diagnosis of appendicitis.
Scoring systems and algorithms have been proposed to aid the diagnosis of acute
appendicitis but have not been widely used. (Table 2,3) [7]
The overall accuracy for diagnosing acute appendicitis is approximately 80%, which
corresponds to a mean false-negative appendectomy rate of 20%. Diagnostic accuracy
varies by sex, with a range of 78%–92% in male and 58%–85% in female patients. These
differences reflect the fact that appendicitis may be extremely difficult to diagnose in
women of childbearing age, because symptoms of acute gynaecologic conditions such as
pelvic inflammatory disease may manifest similarly. This diagnostic problem has led to
false-negative appendectomy rates as high as 47% in female patients aged 10–39 years.
(Table 3)

SYMPTOMS AND SIGNS                            SENSIBILITY               SPECIFICITY
Hyporexia                                      58% to 91%                37% to 40%
Nauseas and vomitings                          40% to 72%                45% to 69%
Diarrhoea                                       9% to 24%                58% to 65%
Fever                                          27% to 74%                50% to 84%
Rebound pain                                   80% to 87%                69% to 78%
Leukocytosis                                   42% to 96%                53% to 76%
C-reactive-protein                             41% to 48%                49% to 57%

Table 3. Sensibility and specificity of symptoms and signs on the diagnosis of acute
appendicitis. [7,30,33]

6.1 Anamnesis
For the majority of patients who present to the emergency department with acute
appendicitis, abdominal pain will be their chief complaint. Those presenting within the first
few hours of onset often describe a poorly defined, constant pain referred to the
periumbilical or epigastric region. Nausea, vomiting, and anorexia occur in varying degrees,
though are usually present in more than 50% of cases in all studies. With disease
progressing as previously outlined, pain becomes well defined and localizes in the right
lower quadrant near McBurney's point. [2]
184                   Inflammatory Diseases – Immunopathology, Clinical and Pharmacological Bases

This classic presentation of acute appendicitis occurs in only one half to two thirds of all
patients. Accordingly, the clinician should not consider it the sine qua non for the diagnosis
of acute appendicitis. A failure to recognize other presentations of acute appendicitis will
lead to a delay in diagnosis and increased patient morbidity. Patients with a retrocaecal
appendix or those presenting in the later months of pregnancy may have pain limited to the
right flank or costovertebral angle. Male patients with a retrocaecal appendix may complain
of right testicular pain. Pelvic or retroileal locations of an inflamed appendix will refer to the
pelvis, rectum, adnexa, or rarely, the left lower quadrant. Subcaecal and pelvic suprapubic
pain and urinary frequency may predominate.

6.2 Physical examination
By far, the most likely physical finding is abdominal tenderness, which occurs in over 95%
of patients with acute appendicitis. Patients often find the right lateral decubitus position
with slight hip flexion as the position of maximal comfort. The abdomen is generally soft
with localized tenderness at or about McBurney's point. [1]
The patient is often flushed, with a dry tongue and an associated faetor oris. Temperature
elevations greater than 1°C are rare until appendiceal inflammation has progressed
transmurally or perforation has occurred. The presence of pyrexia (up to 38°C) with
tachycardia is common. A difference between axillary and rectal temperature higher than 1°C
indicates pelvic inflammation that may be due to appendicitis or other pelvic inflammation.
Abdominal examination reveals localised tenderness and muscular rigidity after localisation
of the pain to the right iliac fossa. Rebound tenderness is present, but should not be elicited
to avoid distressing the patient. Patients often find that movement exacerbates the pain, and
if they are asked to cough the pain will often be localised to the right iliac fossa. Diarrhoea
may be present as a result of irritation of the rectum.
Percussion tenderness, guarding, and rebound tenderness are the most reliable clinical
findings indicating a diagnosis of acute appendicitis. Bowel sounds vary and are more likely
to be diminished or absent with advanced inflammation or perforation. Voluntary muscle
guarding in the right lower quadrant is common and usually precedes localized rebound
tenderness. The follow signs of acute appendicitis are the mostly described, but they occur
in less than 10% of patients with acute appendicitis, and their absence should not prevent
the examiner from establishing an accurate diagnosis: [1,2,7]
-    Blumberg's rebound pain; (Figure 2A)
-    Rovsing's sign - pain that is referred to the area of maximal tenderness during
     percussion or palpation of the left lower quadrant; (Figure 2B)
-    a positive psoas (right lower quadrant pain with extension of the right hip); (Figure 2C)
-    obturator (right lower quadrant pain with flexion and internal rotation of the right hip)
     sign depends on the location of the appendix in relation to these muscles and the degree
     of appendiceal inflammation. (Figure 2D)
Findings on per rectal and vaginal examination may be normal, although tenderness to the
right may be present particularly in a pelvic appendix. Tenderness on rectal examination
may be suggestive but is not diagnostic of appendicitis. However, the utility of rectal
examination in patients with acute appendicitis has been brought into question. Repeated
rectal examinations, especially in children, are burdensome and offer little diagnostic value.
In patients with signs and symptoms consistent with a classic presentation of acute
appendicitis, rectal examination offers little toward furthering diagnostic accuracy. Rectal
examination should be reserved for those in whom pelvic or uterine pathology is suspected,
or in atypical presentations that suggest pelvic or retrocaecal appendicitis. [1]
Acute Appendicitis – Propedeutics and Diagnosis                                                 185

A                                                   B

C                                                             D
Fig. 2. Physical exam of a patient with right abdominal pain.
A) Blumberg's sign. B) Rovsing's sign. C) Psoas sign. D) Obturator sign.

6.3 Laboratorial findings
There is not a single laboratory marker for discriminating acute appendicitis from other
causes of abdominal pain. Laboratory data upon presentation usually reveal a mildly
elevated leukocytosis with a left shift. The white blood cell (WBC) count is elevated (greater
than 10,000/mm3) in 70% to 90% of patients with acute appendicitis. Likewise, neutrophilia
greater than 75% will occur in the majority of cases. Similar results have been found in
paediatric elderly, and pregnant patients with acute appendicitis. This is not true for elderly,
immunocompromised patients, with conditions such as malignancy or AIDS; leukocytosis is
observed in only 12% and 14% of such patients. [1]
The WBC count is elevated in many other intra-abdominal disease processes, however, both
surgical (i.e., cholecystitis, intestinal obstruction) and nonsurgical (i.e., gastroenteritis, pelvic
inflammatory disease). Although statistically significant differences exist between WBC
elevation observed in appendicitis and that observed in mesenteric adenitis, gastroenteritis,
and abdominal pain of unknown cause, the usefulness of these differences in the evaluation
of any individual patient is minimal.
186                  Inflammatory Diseases – Immunopathology, Clinical and Pharmacological Bases

Measurement of C-reactive protein (CRP), an acute phase reactant, has been studied. The
normal value of C reactive protein is < 15 mg / l and in acute appendicitis is > 25 mg / l. In
presence of gangrenous appendicitis is > 55 mg / l and of perforated appendicitis is
> 66 mg / l. An elevated CRP appears to have a sensitivity of 47% to 75% and specificity of
56% to 82% in acute appendicitis. The CRP is most likely to be elevated in appendicitis if
symptoms are present for more than 12 hours. Interestingly, the combination of an elevated
CRP, elevated WBC, or neutrophilia greater than 75% improves the sensitivity to 97% to
100% for the diagnosis of acute appendicitis. Thus, for patients with normal values for all
three studies, the likelihood of acute appendicitis would be low.
It has been shown that monitoring the blood level of serotonin or 5-hydroxytryptamine
(5HT) is a useful test in the diagnosis of appendicitis. During inflammation,
enterochromaffin cells in the appendix secrete serotonin, and 5-hydroxyindoleacetic acid
(5-HIAA), a serotonin metabolite excreted in urine, has been found to be elevated in
patients presenting with acute appendicitis. Serotonin is one of the key signalling
molecules in the gut. Plasma serotonin rapidly changes to 5-hydroxy-indole-acetic acid in
the liver. Measuring the urinary level of this metabolite is a reliable test especially in the
early diagnosis of inflammation in appendicitis. An early study revealed plasma 5-HT to
have a sensitivity of 58% to 98% and 48% to 100 % specificity in adults within the first 48
hours of symptoms, suggestive of acute appendicitis. However, there was also a high
correlation between urinary 5-HIAA levels and diarrheal illnesses, confounding the
interpretation of 5-HIAA levels in patients presenting with abdominal pain and diarrhoea.
In addition, gangrenous appendices had similar urinary 5-HIAA levels to normal
appendices, thought to arise from the destruction of enterochromaffin cells in gangrenous
cases. [19,20,21]
Several studies have demonstrated significant increases in other inflammatory markers,
such serum interleukin 6, and serum phospholipid A2, in cases of acute appendicitis. The
low specificity of many of these laboratory markers and high false-positive and negative
rates prevent useful interpretation of them in discriminating acute appendicitis.
Pregnancy test should also be considered in special cases, to exclude pregnancy. Cultures
of the peritoneal fluid during appendectomy have been shown to be of no benefit. [2,
The urinalysis is abnormal in 19% to 40% of patients with acute appendicitis. Women have a
higher incidence of abnormal urinalysis than men in acute appendicitis. Abnormalities
include mild pyuria, bacteriuria, and haematuria. However, the presence of more than 30
red blood cells or more than 20 WBCs should cause the clinician to consider urinary tract
disease in the differential diagnosis.

6.4 Imaginological findings
Imaginological investigations should be done only in patients in whom a clinical and
laboratorial diagnosis of appendicitis cannot be made. The impact of the introduction of
imaging techniques on the negative appendectomy rate is unclear. A longitudinal study has
suggested that despite the introduction of ultrasonography and computed tomography
scanning the rates of negative appendectomy have remained unchanged. However, other
studies have evaluated the use of ultrasonography and computed tomography, and both
showed a decrease in the number of unnecessary admissions and appendectomies. (Table 4)
Acute Appendicitis – Propedeutics and Diagnosis                                           187

                                                                   POSITIVE NEGATIVE
Abdominal radiography *                  97.05%       85.33%         78.94%     98.08%
Ultrasound                              44% - 90%    47% - 95%      89% - 94% 89% - 97%
Computed tomography                     72% - 97%    91% - 99%      92% - 98% 95% - 100%
Scintigraphy                            91% - 98%    91% - 99%

* Faecal loading image in the caecum.
Table 4. Accuracy of the images for the diagnosis of acute appendicitis. [7,8,35,36,37]


188                  Inflammatory Diseases – Immunopathology, Clinical and Pharmacological Bases


Fig. 3. Abdominal images of appendicitis.
A) Abdominal plain radiography showing distension of the caecum with faecal loading image.
B) Abdominal ultrasound showing an enlarged appendix with a thick wall.
C) Doppler ultrasound showing an inflamed appendix
D) Computed tomography of a patient with appendicitis. Observe the faecal loading in the

6.4.1 Radiography
Plain abdominal radiographs are abnormal in 24% to 95% of patients with appendicitis,
depending on the method of the study. Radiographic signs suggestive of appendicitis
Acute Appendicitis – Propedeutics and Diagnosis                                             189

include appendiceal faecalith; gas in the appendix; air-fluid levels or distension of the
terminal ileum, caecum, or ascending colon (signs of localized paralytic ileum); loss of the
caecal shadow; blurring or obliteration of the right psoas muscle; rightward scoliosis of
the lumbar spine; density or haziness over the right sacroiliac joint; and free
intraperitoneal air or fluid. Of these, localised ileus appears to be the most common
radiographic finding. Although much is made of the presence of localized adynamic
ileum, a calcified faecalith (appendicolith), deformity of the caecum and increase in soft
tissue density in the lower quadrant, they are present in only a minority of patients with
acute appendicitis.
A calcified appendicolith is visualized on an abdominal film in 13% to 22% of patients with
acute appendicitis; however, the likelihood of perforation has been shown to be significant
(45% to 100%) if this radiographic finding is visualized. Similarly, nonspecific findings of an
ileum may also be identified. None of the above radiographic signs are diagnostic or specific
for appendicitis and have been observed in 38% to 60% of patients without appendicitis.
(Table 5) [1,2,34,35,36,37]
In presence of acute pain, abdominal plain abdominal radiography is relevant and helpful,
but little significance is attached to this exam in appendicitis. In fact the radiological signs
described in the literature are not constant and none of them is specific for acute
appendicitis. [35,36,37]
Since 1999, we have studying a new radiological sign, characterized by faecal loading image
in the caecum. In a study, with 460 patients with confirmed appendicitis, we verified this
radiological sign has a sensitivity of 97 % and a specificity of 85% when compared with
other inflammatory conditions of the right abdomen, such as cholecystitis, pelvic
inflammatory diseases and nephrolithiasis. Another important finding is the negative
predictive value that is 98%. Thus in the absence of faecal loading image in the caecum, the
possibility of acute appendicitis is 1%. This sign disappears during the first day after
appendectomy in 94% of patients. (Figure 3A) [35,36,37]
This sign seems to be due to the caecal localised ileum, provoked by the inflammatory
process. The caecal content is storaged and cannot be conducted to the right colon since little
movement occurs in the caecum. This condition lead to enlargement of the caecum and
presence of faecal loading identified at the plain abdominal radiography. (Figure 3A)

RADIOGRAPHIC SIGNS                                                     SENSIBLITY (%)
Faecal loading image in the caecum                                          97,05
Localized adynamic ileum                                                  15 to 55
Image of increasing in soft tissue density                                12 to 33
Image of air inside the appendix                                             <2
Appendicoliths                                                             7 to 22
Lumbar scoliosis                                                           1 to 14
Disappearance of caecal image                                               1 to 8
Deformity of the caecum                                                     4 to 5

Table 5. Sensibility (percentage) of radiographic findings on diagnosis of acute appendicitis.
190                   Inflammatory Diseases – Immunopathology, Clinical and Pharmacological Bases

6.4.2 Ultrasound (US)
Puylaert proposed the sonographic graded compression technique for diagnosis of
appendicitis in 1986. US is rapid, non-invasive, inexpensive, and requires no patient
preparation or contrast material administration. Because US involves no ionizing radiation
and excels in the depiction of acute gynaecologic conditions, it is recommended as the initial
imaging study in children, in young women, and during pregnancy. [8,38,39]
Although operator skill is an important factor in all US examinations, it has particular
importance in the examination of the patient with right-lower-quadrant pain. The learning
curve required to develop the technique for scanning the right lower quadrant is
considerable, and there are many pitfalls to be aware of. Nonetheless, the criteria for the US-
based diagnosis of acute appendicitis are well established and reliable. In experienced
hands, US has reported sensitivities of 75% to 90%, specificities of 86% to 100%, accuracies of
87% to 96%, positive predictive values of 91% to 94%, and negative predictive values of 89%
to 97% for the diagnosis of acute appendicitis. [3,8,14,18,38,39,40]
US examination of the patient suspected to have appendicitis should include a thorough
evaluation of both the abdomen and the pelvic organs. In women in whom the answer is not
evident after the performance of these two examinations, endovaginal US should be added.
This is of particular importance if one considers the overlap in the symptoms of appendicitis
with those of gynaecologic disease in women in the childbearing years. A gynaecologic
explanation for the symptoms may be evident on the endovaginal images. Conversely, the
appendix may have a pelvic location, in which case it may be seen clearly on the
endovaginal image when it is not evident on the suprapubic image. [8]
The specific US approach to the right lower quadrant should include graded compression
US. Putting the patient in left lateral decubitus position may be helpful in visualizing a
retrocaecal appendix. Normal and gas-filled loops of gut will be either displaced from the
field of view or compressed between the layers of musculature of the anterior and the
posterior abdominal walls. In contrast, abnormal loops of gut, or the obstructed appendix,
will be non-compressible and optimally seen on the graded compression image.
The appendix appears on ultrasound as a lamellated, elongated, blind-ending structure.
Unlike normal bowel, the inflamed appendix is fixed, non-compressible, and appears round
on transverse images. Measurements of appendix are performed with full compression.
Traditionally, the diagnosis of appendicitis is made when the diameter of the compressed
appendix exceeds 6 mm In contrast, the thick-walled and non-compressible appendix,
maintained in a fixed position by the compressing transducer, will show circumferential
colour when inflamed. Appendiceal perforation can be diagnosed when the appendix
demonstrates irregular contour or when periappendiceal fluid collections are identified.
Appendicoliths are seen in 30% of appendicitis cases and may confer a higher risk of
perforation. (Figure 3B) [8,38,39,40]

6.4.3 Doppler Ultrasound
The addition of colour Doppler US also is of benefit in the evaluation of inflammatory
conditions of the intestinal tract. The activity of inflammation is proportional to the amount
of colour signal detected within the gut wall. The normal gut is thin walled and compliant
and frequently shows peristaltic activity. Hence, the detection of colour Doppler ultrasound
signals from the normal gut is extremely difficult. [8,40]
Doppler examination usually reveals increased vascularity in and around the acutely
inflamed appendix. Doppler examination is useful as an adjunct sign of appendicitis when
Acute Appendicitis – Propedeutics and Diagnosis                                           191

the appendiceal measurement is equivocal, in which it is uncertain as to whether the imaged
appendix is normal or inflamed. When increased flow is seen, it is a sensitive sign of
appendicitis (reported sensitivity of 87%), but blood flow decreases in advanced
inflammation, when intraluminal pressures exceed perfusion pressures. Doppler signal is
diminished when the appendix is gangrenous or close to necrosis. Therefore, Doppler
examination cannot reliably distinguish between normal and abnormal appendix. (Figure
3C) [8, 18,38,39,40]

6.4.4 Computed Tomography (CT)
CT represents an excellent diagnostic alternative for all other patients. CT is complementary
to US and is recommended whenever US results are suboptimal, indeterminate, or normal
in patients with acute abdominal pain. US is also complementary to CT and may be
particularly useful in thin patients in whom the results of initial CT, no matter how it is
performed, are equivocal. CT to be superior to graded compression US in the diagnosis of
acute appendicitis. Analysis of the data for CT and US revealed similar specificities (89% vs
91%, respectively) and positive predictive values (96% vs 95%, respectively); however, CT
demonstrated higher sensitivity (96% vs 76%), accuracy (94% vs 83%), and negative
predictive value (95% vs 76%). CT was shown to be more accurate in staging
periappendiceal inflammation, more useful in diagnosing acute abdominal conditions
unrelated to appendicitis, and more sensitive in demonstrating a normal appendix and in
excluding acute appendicitis from the differential diagnosis. [2,6,8,28,38,39,40,41]
CT is a highly accurate and effective cross-sectional imaging technique for diagnosing and
staging acute appendicitis. CT is readily available, is operator-independent, is relatively
easy to perform, and has results that are easy to interpret. Moreover, extremes of body
habitus rarely limit study acquisition or interpretation when optimized scanning methods
are used. [8]
Helical CT has reported sensitivities of 90% to 100%, specificities of 91% to 99%, accuracies
of 94% to 98%, positive predictive values of 92% to 98%, and negative predictive values of
95% to 100% for the diagnosis of acute appendicitis. These results are comparable to those
achieved by experienced investigators who have used thin-section, conventional, contrast
material-enhanced CT and are superior to recently reported clinical accuracy. The diagnostic
accuracy of non-contrast CT for the diagnosis of acute appendicitis in the adult population is
adequate for clinical decision making. [2,6,8,28,38,39,40,41]
Appendiceal CT protocols differ considerably with regard to the anatomic area to be
included in the scan and to the use of intravenously, orally, and rectally administered
contrast material. The most popular and conservative approach is to perform helical CT
scanning of the entire abdomen and pelvis with intravenous and oral contrast material.
Proponents of this technique believe that contrast-enhanced CT is essential in the diagnosis
and staging of numerous inflammatory, ischemic, and neoplasic processes that may cause
acute abdominal pain and may simulate appendicitis.
The best results are achieved when the caecum is opacified by contrast, allowing detection
of secondary colonic pathology. To take advantage of oral contrast in this way, one must
wait one hour or more after administration of oral contrast to image the patient. This delay
is the main disadvantage of this protocol, although it is unclear if it is long enough to
adversely effect outcomes.
An alternative involves administration of rectal contrast and scanning only the lower
abdomen (below the lower pole of the right kidney) and upper pelvis. The reported
sensitivity, specificity, and accuracy of this technique are 98%. The inflamed appendix
192                   Inflammatory Diseases – Immunopathology, Clinical and Pharmacological Bases

usually does not fill with rectal contrast or gas, but if the point of obstruction is not at the
base, a small amount of fluid or contrast can leak into the proximal portion of the appendix.
Gas also may be present within the inflammed appendix because of the presence of gas-
forming micro-organisms. [8,18,38,40]
The fastest CT protocol uses a non-enhanced helical CT of the entire abdomen and pelvis.
This examination may be performed in 10 minutes, does not expose the patient to the
potential risks associated with iodinated contrast agents, requires no bowel preparation, and
represents the most cost-effective imaging alternative to US. This procedure is most effective
in patients with large body habitus, as diagnostic accuracy may be compromised in patients
with little abdominal and intrapelvic fat. These investigators have shown that non-enhanced
CT is an accurate technique for establishing an alternative diagnosis in patients suspected to
have appendicitis. [8,40,41]
When seen, the normal appendix appears as a tubular or ringlike peri-caecal structure that is
either totally collapsed or partially filled with fluid, contrast material, or air. The normal
appendiceal wall measures less than 1–2 mm in thickness. The periappendiceal fat should
appear homogeneous, although a thin mesoappendix may be present. The inflamed
appendix appears as an enlarged blind-ending tubular structure, frequently associated with
inflammatory stranding in the surrounding fat. Identification of the appendix is possible
with most of the modern CT protocols. The entire appendix should be examined, from
caecal insertion to the tip, and the largest transverse diameter should be reported.
Traditionally, the threshold diameter of 6 mm was used for diagnosis of appendicitis.
However, studies of healthy adults revealed that the normal range of appendiceal size in an
adult patient is 3 to 10 mm. Thus, using an appendiceal threshold size of 9 mm is more
accurate for diagnosis of appendicitis. (Figure 3D) [8]
A definitive CT diagnosis of acute appendicitis can be made if an abnormal appendix is
identified or if a calcified appendicolith is seen in association with peri-caecal inflammation.
The appearance of the abnormal appendix varies with the stage and severity of the disease
process. In patients with mild, non-perforating appendicitis who undergo scanning shortly
after the onset of symptoms, the appendix may appear as a minimally distended, fluid-
filled, tubular structure 5 to 6 mm in diameter surrounded by the homogeneous fat
attenuation of the normal mesentery. This appearance is seen in only the most incipient
forms of acute appendicitis and, in our experience, occurs in fewer than 5% of patients who
undergo scanning. The signs of perforated appendicitis include phlegmon, abscess,
extraluminal gas, extraluminal appendicolith, and focal defect in the enhancement of the
appendiceal wall. [2,8]

6.4.5 Magnetic Resonance (MR)
MR imaging is emerging as an alternative to CT in pregnant patients and in patients who
have an allergy to iodinated contrast material. MR imaging has a limited role in the work-up
of suspected appendicitis. Although the use of MR imaging avoids ionizing radiation, it has
several disadvantages, including high cost, long duration of studies, and limited availability
on an emergent basis. According some authors, the use of MR imaging is limited to
pregnant patients in whom ultrasound is inconclusive.
There are no known adverse effects of MR imaging in human pregnancy, but the safety of
MR imaging has not been proven unequivocally. Although tissue heating from
radiofrequency pulses, acoustic stimulation potentially harm the foetus. It remains there for
an indefinite amount of time, excreted by the foetal kidneys and subsequently swallowed by
the foetus with amniotic fluid. Although there is no evidence of mutagenic or teratogenic
Acute Appendicitis – Propedeutics and Diagnosis                                              193

effects of gadolinium in humans, mutagenic effects were seen in animal studies. Therefore a
conservative approach avoids using gadolinium when possible in the first trimester.[40]
On MR imaging, the appendix is identified as a tubular structure with intraluminal T1 and
T2 prolongation. Appendicitis is diagnosed using thresholds of the size used for CT.
Inflammatory changes are visualized as T2 hyperintensity in the periappendiceal fat. In
pregnant women, the abdomen must be examined carefully for an unusual location of the
appendix because pregnant uterus displaces the appendix significantly.

6.4.6 Scintigraphy
An inflamed bowel has strong chemotactic properties, and leukocytes actively invade the
appendix in acute appendicitis. The migration and accumulation of radioactive leukocytes
in the appendix is the basis for this study in patients believed to have acute appendicitis.
Indium-111–labelled leukocyte scanning had a sensitivity of 86% and specificity of 93% for
the diagnosis of acute appendicitis. Although the majority of these scans were performed at
2 hours after injection, occasionally delayed images up to 17 to 24 hours were required.
Technetium-99m-albumin–colloid–labelled leukocyte (TAC-WBC) scanning appears to be
superior to indium-111 because it is less expensive, requires shorter preparation time,
requires less delay in time to positive scan (within 2 hours), and has a lower radiation-
absorbed dose, compared with indium-111. The overall sensitivity of this method is of 89%
and its specificity is of 92% It is not reliable in diagnosing appendicitis in women, with only
a 75% sensitivity and 43% positive predictive value in this subgroup. Limitations of
radionuclide-labelled leukocyte scanning include cost, delay in diagnosis, exposure to
radiation, relatively large percentage of indeterminant scans, and decreased sensitivity and
specificity in women. [1]

7. Differential diagnosis
The differential diagnosis of appendicitis is that of an acute abdomen. At the extremes of
age, the threshold for referral for further assessment should be low because of the high
mortality associated with delayed presentation or diagnosis. Traditionally, a high negative

FREQUENT                                     RARE
Acute gastroenteritis                        Epiploic appendagitis
Acute mesenteric adenitis                    Acute pancreatitis
Acute cholecystitis                          Colonic and appendiceal diverticulitis
Intestinal intussusceptions (children)       Intestinal obstruction
Perforated peptic ulcer                      Crohn's disease
Meckel's diverticulitis                      Yersiniosis
Rectus sheath haematoma                      Henoch-Schönlein purpura
Right Spighelian hernia                      Diabetic ketoacidosis
Urinary tract infection                      Right pyelonephritis
Right uretheral stone                        Right pneumonia
Ruptured right Graafian follicle             Ruptured ectopic pregnancy
Right salpingitis                            Pain on the right 10th and 11th dorsal nerves
Endometriosis                                Porphyria
Ovarian torsion                              Other abdominal inflammatory conditions
Table 6. Differential diagnosis of acute appendicitis. [6,7]
194                   Inflammatory Diseases – Immunopathology, Clinical and Pharmacological Bases

appendectomy rate of 10% to 20% has been considered acceptable to minimize the number
of missed cases of appendicitis. However, removal of a normal appendix is associated with
an early complication rate of 7% to 13% and a late complication rate of 4%, hence, it is not a
benign procedure. The clinical presentation of acute appendicitis is often atypical and may
mimic other abdominal conditions, confounding its clinical diagnosis and resulting in a
clinical diagnostic accuracy of only 60% to 80%. (Table 6) [6,7]

8. Complications
Any delay of time for treating acute appendicitis is unwarranted. When the total time
interval of symptoms was less than 12 hours, 94% of patients had simple appendicitis, but
6% had perforation. Rupture rates rise significantly 36 hours after presentation symptoms.
The overall incidence of perforation is 16% to 39%. Perforation rates are strongly age related
and are highest in the very young (40% to 57%) and in the elderly (55% to 70%), in whom
misdiagnosis and delayed diagnosis are common. The relationship between diagnostic
accuracy and perforation remains controversial. (Figure 4D) [3,5,8,11]
In patients with a delayed presentation, a tender mass with overlying muscle rigidity may
be felt in the right iliac fossa. The presence of a mass may be confirmed on ultrasonography
or computed tomography scan; underlying neoplasm must be excluded, especially in
elderly people. [7]
Patients with an appendix abscess have a tender mass with a swinging pyrexia, tachycardia,
and leukocytosis. The abscess is most often located in the lateral aspect of the right iliac
fossa but may be pelvic; a rectal examination is useful to identify a pelvic collection. The
abscess can be shown by ultrasonography or computed tomography scanning, and a
percutaneous radiological drainage may be done. Open drainage has the added advantage
of allowing an appendectomy to be done.[5,7]
A history of appendectomy is associated with delayed onset of disease and a less severe
disease phenotype in patients with ulcerative colitis. The influence of appendectomy in
Crohn's disease is not as clear; some evidence suggests a delayed onset of disease in patients
after appendectomy, although contradictory evidence also exists to suggest an increased risk
of developing the condition depending on the patient's age, sex, and diagnosis at the time of
operation. There are circumstantial reports that suggest association between inflammatory
bowel or intestinal cancer and appendicitis. However there is no scientific evidence of such an
association. Otherwise, chronic appendicitis does not seem to represent any risk of cancer. [7]

9. Therapeutic decisions
Appropriate care followed by expedient appendectomy is the treatment of choice. No
evidence exists to support the notion that analgesia should be withheld on the grounds that
it may cloud the clinical picture. All patients should receive broad spectrum perioperative
antibiotics (one to three doses), as they have been shown to decrease the incidence of
postoperative wound infection and intra-abdominal abscess formation. [7,42]
According to some authors, the initial nonoperative management of these patients has been
established as safe and effective, and is likely the preferred method of treatment. [29,43]

9.1 Non-operative treatment
Non-operative management with antibiotics has been established for the treatment of
uncomplicated diverticulitis, salpingitis, enterocolitis and other abdominal inflammatory
Acute Appendicitis – Propedeutics and Diagnosis                                           195

diseases. It is surprising that non-operative management of uncomplicated acute
appendicitis remains largely unexplored despite evidence that uncomplicated acute
appendicitis often resolves, either spontaneously or with antibiotic therapy, and has been
shown by limited studies to have outcomes equivalent to those of appendectomy.
Evidence suggests that spontaneous resolution of untreated, non-perforated appendicitis is
common and that perforation can be prevented. This motivates a shift in focus from the
prevention of perforation to the early detection and treatment of advanced appendicitis. In
patients with an equivocal diagnosis where advanced appendicitis is deemed less likely a
correct diagnosis is more important than a rapid diagnosis. These patients can safely be
managed by active observation with an improved diagnostic work-up under observation.
Appendicitis can be treated non-operatively with IV antibiotics with the performance of
percutaneous drainage if an abscess is present. There are several schemes of antibiotics
(usually cefoxitin and gentamicin or trimethoprim/sulfamethoxazole and metronidazole)
described in the literature, all of them with good results. (Table 7) [17,42]
Success rates have been reported as between 88% and 100%, with the incidence of recurrent
appendicitis 5% to 38%. The protocol for suspected acute appendicitis consists of bowel rest
and parenteral fluids. Antibiotics active against gram-negative and anaerobic organisms
should be administered. Initial successful nonoperative management is achieved in 95% of
patients. The incidence of progression to diffuse peritonitis during nonoperative treatment
for palpable periappendiceal mass is 0.6% to 5%. Progression to peritonitis is a concern,
because patients without a palpable mass may not have developed localization and isolation
of appendicitis. This condition is more frequent in elders and in immunossupressed
patients, such as those in use of steroids, chemotherapy, etc. These patients should not been
included in non-operative protocols. [16,29,40,43,44]
Over the initial 48 to 72 hours of hospitalization, the patients must be serially examined. If
the patient’s abdominal examination deteriorated or if the patient subjectively or objectively
did not improve, percutaneous abscess drainage is undertaken if possible. If a fluid
collection amenable to drainage did not exist, urgent appendectomy is undertaken. If the
patient improved, parenteral antibiotics are continued until the patient remained afebrile for
24 hours. The average length of hospitalization is one week. [29]

AUTHOR                          ANTIBIOTIC (IV)                SUCCESS RECURRENCE
Coldrey (1959)                  Penicillin + streptomycin         92        14
Adams (1990)                    Clindamycin + gentamicin            56             13
Eriksson, Granstrom (1995)      Cefotaxime + tinidazole             95             35
Winn et al. (2004)              Gentamicin + metronidazole          92              5
Styrud et al. (2006)            Cefotaxime + tinidazole (IV)        88             14
Table 7. Clinical studies documenting success and recurrence (percentages) of non-operative
management (with antibiotics) of uncomplicated acute appendicitis. [15,16,17,29,40]

9.2 Operative treatment
The treatment of appendicitis depends on both the patient’s general condition and the state
of the appendix. Traditionally, open appendectomy has been done through a muscle
196                   Inflammatory Diseases – Immunopathology, Clinical and Pharmacological Bases

splitting gridiron incision over McBurney's point made perpendicular to a line joining the
umbilicus and anterior superior iliac spine or through a more cosmetically acceptable Lanz's
incision. The proportion of open procedures done has fallen with the increased use of
laparoscopic techniques. The use of drains has not proved useful except perhaps in cases of
walled-off abscess cavities. [23] When the process is spread as a general peritonitis, a
median or a right medial paramedian pararectal incision are indicated, in order to aspirate
the septic secretion and to treat all complications. Abdominal drainage did not prove to
have any benefit. [45]
Since the advent of laparoscopic surgery for appendectomy in 1983, its use has steadily
increased through the past decade. Laparoscopy is now the standard method of
investigating acute lower abdominal pain. If appendectomy is considered necessary, then it
is logical to remove the appendix using laparoscopic techniques. The proposed advantages
of laparoscopic compared with open appendectomy have seemed less compelling than
laparoscopy in other abdominal procedures, and many surgeons still favour open repair
because they believe that the overall morbidity is primarily a function of the degree of
appendicitis. Compared with open surgery, a systematic review found that laparoscopic
appendectomy in adults reduces wound infections, postoperative pain, length of hospital
stay, and time taken to return to work. In children, laparoscopic appendectomy reduced the
number of wound infections and the length of hospital stay compared with open surgery,
but no significant differences in postoperative pain, time to mobilisation, or proportion of
intra-abdominal abscesses were seen. [13,45,46,47,48]
With advances in laparoscopic instruments and skills, laparoscopic single-port surgery has
been developed and applied to appendectomy. It offers better cosmetic results (scarless
abdominal surgery via umbilical incision), less incisional pain, and the capability to convert
to multiport surgery if required. [49,50,51,52,53,54,55]

9.3 Perioperative period
Children with appendicitis are often dehydrated and may be febrile, acidotic, and septic.
Intravenous fluids and antibiotics are always indicated preoperatively. All the patients
followed the same preoperative protocol, with antibiotic prophylaxis before the operation
and postoperative antibiotic treatment according to the macroscopic characteristics of the
appendix and whether purulent free liquid into the abdominal cavity was present or not.
The antibiotic regimen selected should be effective against the bacterial flora found in the
appendix, which consists chiefly of anaerobes and gram-negative coliforms. Anaerobes
make up most of the colonic flora and include Bacteroides, Clostridial, and Peptostreptococcus
species. Gram-negative aerobes, such as Escherichia coli, Pseudomonas aeruginosa, Enterobacter,
and Klebsiella, are also important. Gram-positive organisms are less commonly found in the
colon, and the need for coverage for them (primarily Enterococcus) is controversial.
For non-perforated appendicitis, a single agent such as cefoxitin, cefotetan,
ampicillin/sulbactam, ticarcillin/clavulanate, or piperacillin/tazobactam is typically
prescribed. In cases of perforated appendicitis, most surgeons select either traditional
“triple” antibiotics (ampicillin, gentamycin, and clindamycin or metronidozole or
piperacillin/tazobactam) or a combination such as ceftriaxone/metronidozole or
ticarcillin/clavulante plus gentamycin. [11,14,42]
Appendectomy is a relatively safe procedure with a mortality rate for non-perforated
appendicitis of 0.8 per 1000. The mortality and morbidity are related to the stage of disease
Acute Appendicitis – Propedeutics and Diagnosis                                          197

and increase in cases of perforation; mortality after perforation is 5.1 per 1000. As stated
above, the average rate of perforation at presentation is between 16% and 30%, but this is
significantly increased in elderly people and young children, in whom the rate can be up to
97%, usually because of a delay in diagnosis. Wound complications, ileum, and partial small
bowel obstruction are the most common complications. [7,29]
The increased mortality and morbidity associated with perforation has been used as
justification for high rates of negative appendectomy, quoted as between 20% and 25%.
Despite this, complications can occur after removal of a normal appendix, and the surgical
community continues to strive to reduce the numbers of negative procedures. According to
a large historical cohort study, a perforated appendix during childhood does not seem to
have a long term detrimental effect on subsequent female fertility.
The rate of postoperative wound infection is determined by the intraoperative wound
contamination. Rates of infection vary from < 5% in simple appendicitis to 20% in cases with
perforation and gangrene. The use of perioperative antibiotics has been shown to decrease
the rates of postoperative wound infections. For perforated appendicitis, LA is associated
with a higher rate of intra-abdominal abscess drainage and intraoperative complications
compared with OA. In contrast, there is a trend towards significance for LA to be associated
with lower rates of wound infections and postoperative intestinal obstructions.
Intra-abdominal or pelvic abscesses may form in the postoperative period after gross
contamination of the peritoneal cavity. The patient presents with a swinging pyrexia, and
the diagnosis can be confirmed by ultrasonography or computed tomography scanning.
Abscesses can be treated radiologically with a pigtail drain, although open or per rectal
drainage may be needed for a pelvic abscess. The use of perioperative antibiotics has been
shown to decrease the incidence of abscesses. Male and older patients also had an increased
risk of intra-abdominal abscess drainage. [7,42,45,48,50]
Wound infections are the most common complication, yet they are substantially less
common in children than in adults and may not be related to type or timing of antibiotics or
to the type of postoperative wound management. [14,42]
Mortality from appendectomies has been strongly linked to 2 factors in particular—patient
age and diagnosis at time of surgery. [2,3]
The most common complications found during the early postoperative period are wound
infections and local abscess. After perforated or gangrenous appendicitis subphrenic and
pelvic abscesses may occur as well. Peritonitis fistulas and incisional hernias are
complications provoked by a not well conducted surgery and may be considered iatrogenic
damages that should not occur. All these adverse events are followed by disturbances on the
metabolic response to trauma.

10. Final considerations
The appendix is still a mysterious organ. Despite the over 150 years of intense research and
many thousands researches developed on all fields related to the appendix we still do not
know what is the role of this organ. A hypothesis suggests this organ is turning down and
going to disappear. However this is still a very controversial theory not accepted by most of
investigators. However this is still a very controversial theory not accepted by most of
The pathophysiology of appendicitis is still not established. The theory that ascribes to an
obstructive phenomenon the initial stage of appendicitis was not proved and it is not
198                  Inflammatory Diseases – Immunopathology, Clinical and Pharmacological Bases

possible to provoke appendicitis in an experimental model. We do not have idea about the
role of the enterochromaffin cells in the appendix. Adenocarcinoma is the main cancer of all
the digestive system except in the appendix where the characteristic tumour is the carcinoid.
Many other doubts have been proposed without satisfactory response.
Traditionally, when the medicine is not able to understand a disease, the removal of the
organ is indicated. For this reason most of physicians still prefer appendectomy as the best
treatment to heal appendicitis. The advances in technology allowed a safer operations with
aesthetically best results, without complications, and no death is accepted independently the
stage of the inflammation. On the other side even the clinical treatment based on antibiotics
is able to heal this inconvenient disease.
We are not able to preview the future of the studies on appendicitis and its treatment, but
for sure all the investigations will make possible to understand this fascinating organ its
inflammation and indicate the best treatment and even prevent its occurrence.

11. Acknowledgment
The author gratefully thanks Dr. Rogério Augusto Pinto da Silva for the ultrasound images

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                                      Inflammatory Diseases - Immunopathology, Clinical and
                                      Pharmacological Bases
                                      Edited by Dr Mahin Khatami

                                      ISBN 978-953-307-911-0
                                      Hard cover, 396 pages
                                      Publisher InTech
                                      Published online 10, February, 2012
                                      Published in print edition February, 2012

This book is a collection of comprehensive reviews contributed by experts in the diverse fields of acute and
chronic inflammatory diseases, with emphasis on current pharmacological and diagnostic options. Interested
professionals are also encouraged to review the contributions made by experts in a second related book
entitled "Inflammation, Chronic Diseases and Cancer"; it deals with immunobiology, clinical reviews, and
perspectives of the mechanisms of immune inflammatory responses that are involved in alterations of immune
dynamics during the genesis, progression and manifestation of a number of inflammatory diseases and
cancers, as well as perspectives for diagnosis, and treatment or prevention of these disabling and potentially
preventable diseases, particularly for the growing population of older adults around the globe.

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Immunopathology, Clinical and Pharmacological Bases, Dr Mahin Khatami (Ed.), ISBN: 978-953-307-911-0,
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